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Zebrafish Behavioral Profiling Links Drugs to Biological Targets and Rest/Wake Regulation

Rihel, Jason and Prober, David A. and Arvanites, Anthony and Lam, Kelvin and Zimmerman, Steven and Jang, Sumin and Haggarty, Stephen J. and Kokel, David and Rubin, Lee L. and Peterson, Randall T. and Schier, Alexander F. (2010) Zebrafish Behavioral Profiling Links Drugs to Biological Targets and Rest/Wake Regulation. Science, 327 (5963). pp. 348-351. ISSN 0036-8075.

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A major obstacle for the discovery of psychoactive drugs is the inability to predict how small molecules will alter complex behaviors. We report the development and application of a high-throughput, quantitative screen for drugs that alter the behavior of larval zebrafish. We found that the multidimensional nature of observed phenotypes enabled the hierarchical clustering of molecules according to shared behaviors. Behavioral profiling revealed conserved functions of psychotropic molecules and predicted the mechanisms of action of poorly characterized compounds. In addition, behavioral profiling implicated new factors such as ether-a-go-go–related gene (ERG) potassium channels and immunomodulators in the control of rest and locomotor activity. These results demonstrate the power of high-throughput behavioral profiling in zebrafish to discover and characterize psychotropic drugs and to dissect the pharmacology of complex behaviors.

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Prober, David A.0000-0002-7371-4675
Additional Information:© 2010 American Association for the Advancement of Science. Received for publication 8 October 2009. Accepted for publication 11 December 2009. We thank J. Dowling, D. Milan, and G. Vanderlaan for suggestions and reagents and D. Schoppik, G. Uhl, and I. Woods for critical reading of the manuscript. Supported by a Bristol-Myers Squibb postdoctoral fellowship of the Life Sciences Research Foundation (J.R.), a Helen Hay Whitney Foundation postdoctoral fellowship (D.A.P.), a NIH Pathway to Independence grant (D.A.P.), the Stanley Medical Research Institute (S.J.H.), the Harvard Stem Cell Institute (L.L.R.), NIH grants MH086867 and MH085205 (R.T.P.), and grants from NIH and the McKnight Endowment Fund for Neuroscience (A.F.S.). L.L.R. is a founder of iPierian Inc., a biotechnology company, and is a member of its scientific advisory board.
Funding AgencyGrant Number
Bristol-Myers SquibbUNSPECIFIED
Life Sciences Research FoundationUNSPECIFIED
Helen Hay Whitney FoundationUNSPECIFIED
NIH Pathway to IndependenceUNSPECIFIED
Stanley Medical Research InstituteUNSPECIFIED
Harvard Stem Cell InstituteUNSPECIFIED
McKnight Endowment Fund for NeuroscienceUNSPECIFIED
Issue or Number:5963
Record Number:CaltechAUTHORS:20150914-145343001
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Official Citation:Zebrafish Behavioral Profiling Links Drugs to Biological Targets and Rest/Wake Regulation Jason Rihel, David A. Prober, Anthony Arvanites, Kelvin Lam, Steven Zimmerman, Sumin Jang, Stephen J. Haggarty, David Kokel, Lee L. Rubin, Randall T. Peterson, and Alexander F. Schier Science 15 January 2010: 327 (5963), 348-351. [DOI:10.1126/science.1183090]
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:60230
Deposited By: George Porter
Deposited On:15 Sep 2015 14:48
Last Modified:03 Oct 2019 08:54

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